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Troxerutin Prevents 5-Fluorouracil Induced Morphological Changes in the Intestinal Mucosa: Role of Cyclooxygenase-2 Pathway

1
Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro of Farias Street, Porangabuçu Campus, Fortaleza 60416-030, Brazil
2
Nucleus of Research and Development of Medications (NPDM), Federal University of Ceará, Coronel Nunes of Melo Street, 100, Fortaleza 60430-275, Brazil
3
Research Group in Natural Sciences and Biotechnology, Federal University of Maranhão, s/n Avenue Aurila Maria Santos Barros of Sousa, Frei Alberto Beretta, Grajaú-MA 65940-000, Brazil
4
Technological Development Park, Federal University of Ceará, Humberto Monte Avenue, 2977, Pici Campus, Fortaleza 60440-900, Brazil
5
Department of Organic and Inorganic Chemistry, Federal University of Ceará, Pici Campus, Fortaleza 60440-900, Brazil
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2020, 13(1), 10; https://doi.org/10.3390/ph13010010
Received: 6 December 2019 / Revised: 29 December 2019 / Accepted: 4 January 2020 / Published: 8 January 2020
Intestinal mucositis is a common complication associated with 5-fluorouracil (5-FU), a chemotherapeutic agent used for cancer treatment. Troxerutin (TRX), a semi-synthetic flavonoid extracted from Dimorphandra gardneriana, has been reported as a potent antioxidant and anti-inflammatory agent. In the present study, we aimed to evaluate the effect of TRX on 5-FU-induced intestinal mucositis. Swiss mice were randomly divided into seven groups: Saline, 5-FU, TRX-50, TRX-100, TRX-150, Celecoxib (CLX), and CLX + TRX-100. The weight of mice was measured daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis), levels of malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), mast and goblet cell counts, immunohistochemical analysis, and cyclooxygenase-2 (COX-2) activity. Compared to the saline treatment, the 5-FU treatment induced intense weight loss and reduction in villus height. TRX treatment (100 mg/kg) prevented the 5-FU-induced histopathological changes and decreased oxidative stress by decreasing the MDA levels and increasing GSH concentration. TRX attenuated inflammatory process by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. TRX also reversed the depletion of goblet cells. Our findings suggest that TRX at a concentration of 100 mg/kg had chemopreventive effects on 5-FU-induced intestinal mucositis via COX-2 pathway. View Full-Text
Keywords: chemoprevention; inflammation; flavonoid; intestine chemoprevention; inflammation; flavonoid; intestine
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de Miranda, J.A.L.; Martins, C.S.; Fideles, L.S.; Barbosa, M.L.L.; Barreto, J.E.F.; Pimenta, H.B.; Freitas, F.O.R.; Pimentel, P.V.S.; Teixeira, C.S.; Scafuri, A.G.; dos Santos Luciano, M.C.; Araújo, J.L.; Rocha, J.A.; Vieira, I.G.P.; Ricardo, N.M.P.S.; da Silva Campelo, M.; Ribeiro, M.E.N.P.; de Castro Brito, G.A.; Cerqueira, G.S. Troxerutin Prevents 5-Fluorouracil Induced Morphological Changes in the Intestinal Mucosa: Role of Cyclooxygenase-2 Pathway. Pharmaceuticals 2020, 13, 10.

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